Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis  

作　　者：Hao-Jun Xie Ming-jie Jiang Ke Jiang Lin-Quan Tang Qiu-Yan Chen An-Kui Yang Hai-Qiang Mai 

机构地区：[1]Department of Head and Neck,Sun Yat-sen University Cancer Center,Guangzhou 510060,China [2]State Key Laboratory of Oncology in South China,Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,China [3]Departcment of Nasopharyngeal Carcinoma,Sun Yat-sen University Cancer Center,Guangzhou 510060,China

出　　处：《Precision Clinical Medicine》2024年第3期265-278,共14页精准临床医学(英文)

基　　金：supported by grants from the National Key Research and Development Program of China(Grant Nos.2022YFC2505800,2022YFC2705005);the National Natural Science Foundation of China(Grant Nos.32200651,82203776,82203125,82222050,82272739,82272882,82173287,82073003,82003267,82002852);Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2021B1515230002,2022A1515110033);Science and Technology Program of Guangzhou(Grant Nos.202201011561,2023A04J2127);Sun Yat-sen University Clinical Research 5010 Program(Grant Nos.201315,2015021,2017010,2019023);Innovative Research Team of High-level Local Universities in Shanghai(Grant No.SSMU-ZLCX20180500);Postdoctoral Innovative Talent Support Program(Grant No.BX20220361);Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002);Key Youth Teacher Cultivating Program of Sun Yat-sen University(Grant No.20ykzd24),and Fundamental Research Funds for the Central Universities.

摘　　要：Background:Intratumor heterogeneity is common in cancers,with different cell subtypes supporting each other to become more malignant.Nasopharyngeal carcinoma(NPC),a highly metastatic cancer,shows significant heterogeneity among its cells.This study investigates how NpC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules.Methods:Exosomes were purified and characterized.MicroRNA expression was analyzed via sequencing and qRT-PCR.The effects of miR-30a-5p on migration,invasion,and metastasis were evaluated in vitro and in vivo.Its impact on desmoglein glycoprotein(DSG2)was assessed using dual-luciferase assays and Western blotting.Immunohistochemistry(IHc)and statistical modeis linked miR-30a-5p/DSG2levelstopatientprognosis.Results:Different NPC ceil subtypes transmit metastatic potential via exosomes.High-metastatic cells enhance the migration,in-vasion,and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p.Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis.miR-30a-5p may promote metastasis by targeting DsG2 and modulating Wnt signaling.Plasma exosomal miR-30a-5p inversely correlates with DsG2 levels,predicting patient outcomes.Conclusion:High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p,which is a valuable prognostic marker assessable via liquid biopsy.

关 键 词：cell heterogeneity cell communication EXOSOMES METASTASIS nasopharyngeal carcinoma 

分 类 号：R73[医药卫生—肿瘤]